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Predictors of response to neoadjuvant therapy in patients with breast cancer in an underserved population

PREDICTORS OF RESPONSE TO NEOADJUVANT THERAPY IN PATIENTS
WITH BREAST CANCER IN AN UNDERSERVED POPULATION
by
Ying Wang
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
December 2011
Copyright 2011 Ying Wang

Purpose: Neoadjuvant therapy has became the standard of care in locally and advanced breast cancer, and is increasingly being used in early-stage breast cancer. The degree of pathologic response to treatment correlates with long-term outcome. The aims of this study were to identify clinical and pathologic characteristics that associated with pathologic complete response to neoadjuvant therapy and determine if different molecular subtypes of breast cancer respond differently to neoadjuvant treatment in patients with stage II and III breast cancer in an underserved and predominantly minority population. ❧ Methods: Using a single-institution database, 104 patients (82 Hispanics, 22 non-Hispanics) who received neoadjuvant therapy followed by surgery from January 2005 to December 2010 were included in this retrospective study. Patients were treated with chemotherapy alone or with trastuzumab. ER, PR and HER2 status were determined by the diagnostic core biopsy before treatment. Only a subset (n=45) of patients underwent BRCA gene testing. Chi-square or Fisher’s exact test was used to examine associations between pathologic complete response (pCR) and clinical-pathologic factors. Logistic regression analyses were performed to assess each variable contribution to pCR. ❧ Results: The overall pCR rate for this series was 27%. Six factors were associated with pCR in univariate analysis: age ≥50 years at diagnosis (p=0.047), clinical N0 node status (p=0.041), breast-conserving surgery (p<0.001), HER2 positive status (p<0.001), hormone receptor (HR) negative status (p=0.024) and molecular subtype (p=0.001). On multivariate analysis, molecular subtype was found to be an independent predictor of pCR to neoadjuvant therapy. The triple negative and HER2+ subtypes were associated with significantly higher rates of pCR, 23% and 44% respectively, whereas the HR+/HER2- subtypes had a pCR rate of 8.6% (p=0.001). HER2+ patients treated with neoadjuvant trastuzumab showed higher pCR rate than HER2+ patients not treated with neoadjuvant trastuzumab but this was not statistically significant (50% versus 27%; p=0.29). ❧ Conclusion: The pCR rate of this predominantly Hispanic cohort was comparable to results found in other studies. Molecular subtype was an independent predictive marker of pCR to preoperative therapy. The triple negative and HER2+ subtypes of breast cancer were significantly sensitive to preoperative therapy than the HR+/HER2- cancers. Addition of neoadjuvant trastuzumab for HER2+ tumors resulted in a superior response.

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PREDICTORS OF RESPONSE TO NEOADJUVANT THERAPY IN PATIENTS
WITH BREAST CANCER IN AN UNDERSERVED POPULATION
by
Ying Wang
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
December 2011
Copyright 2011 Ying Wang